Bruin, Gerardus and Walles, Markus (2022) Absorption, Distribution, Metabolism, and Excretion (ADME) of Therapeutic Proteins: A White Paper on Current Industry Practices and Future Perspectives. Drug metabolism and disposition. ISSN doi: 10.1124/dmd.121.000461

Abstract

Therapeutics proteins (TPs) comprise a variety of modalities including antibody-based drugs, coagulation factors, recombinant cytokines, enzymes, growth factors, and hormones to name a few. TPs usually cannot traverse cellular barriers and exert their pharmacological activity by interacting with targets on the exterior membrane of cells or with soluble ligands in the tissue interstitial fluid/blood. Due to large size, lack of cellular permeability, variation in metabolic fate, and distinct physicochemical characteristics, TPs are subjected to different absorption, distribution, metabolism, and excretion (ADME) processes as compared to small molecules. Limited regulatory guidance makes it challenging to determine the most relevant ADME data required for regulatory submissions. The TP ADME working group (WG) was sponsored by the Translational and ADME Sciences Leadership Group (TALG) within the Innovation and Quality (IQ) consortium with objectives to: i) better understand the current practices of ADME data generated for TPs across IQ member companies, ii) learn about their regulatory strategy and interaction experiences, and iii) provide recommendations on best practices for conducting ADME studies. To understand current ADME practices and regulatory strategies, an industry-wide survey was conducted within IQ member companies. In addition, ADME data submitted to FDA was also collated by reviewing regulatory submission packages of TPs approved between 2011-2020. This article summarizes the key learnings from the survey and an overview ADME data presented in BLAs along with future perspectives and recommendations for conducting ADME studies for internal decision making as well as regulatory submissions for TPs.

Item Type:	Article
Keywords:	ADME of therapeutic proteins
Date Deposited:	11 Mar 2022 00:45
Last Modified:	11 Mar 2022 00:45
URI:	https://oak.novartis.com/id/eprint/45657